Expertise

Prof Portoghese's research focus has been in the area of opioids and opioid receptors. Concurrent with his research activities, he has served as Editor-in-Chief of the Journal of Medicinal Chemistry (1972-2011) for the American Chemical Society. With graduate faculty appointments in Pharmacology and Neuroscience in addition to his home Department, he has ongoing research collaborations in these departments and elsewhere at the University of Minnesota Academic Health Center. Some of the major contributions of Prof Portoghese's research group have been based on the development of concepts that relate to the interaction of opioid ligands with opioid receptors. The multiple modality concept based on the structure-activity relationships of opioid ligands led to the proposal of multiple opioid receptors (1965), which at that time was a departure from the prevailing view of a single receptor type. His group developed selective opioid antagonists such a BFNA (u), nor-BNI (k), and naltrindole (o) that presently are standards for the three opioid receptor types employed in opioid research. His initial studies with bivalent ligands that contain two mu opioid pharmacophores, led to the first propose mu opioid receptor dimers (1982). With the first report (1999) opioid receptor heterodimers (heteromer) by others, Prof Poroghese's research veered to the design of ligands that recognize opioid receptor heteromers, that is the theme of his current research. In this regard, his group has focused on bivalent ligands as agents to study or treat pain associated with neuropathy. This approach has led to the recent development of bivalent ligands (MMG22, MCC22) that produce profound antinociception (fmol ED50 range) without tolerance in the treatment of neuropathic pain.

Professional Associations

American Chemical Society

Research

Research Summary/Interests

Prof. Portoghese’s laboratory is focused on the design and synthesis of compounds that target opioid receptors, both as pharmacologic tools and as agents for treatment of pain. Novel concepts and approaches are employed for development of analgesics that are highly selective for different types of opioid receptors. These studies have utilized animal studies, cloned receptors and molecular modeling as an aid to obtain insight into the recognition of ligands by opioid receptors.